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Bone Marrow Precursor Cells from Aged Mice Generate CD4 T Cells That Function Well in Primary and Memory Responses¹

Trudeau Institute, Saranac Lake, NY 12983

Understanding how aging impacts the function of memory CD4 T cells is critical for designing effective vaccines. Our studies show that immunological memory generated during youth functions well into old age, whereas that generated later in life functions poorly. This is the result of declines in the function of naive CD4 T cells from aged individuals and contributes to reduced efficacy of vaccines in the elderly. To begin to identify the cause of this defect, we examined the function of memory T cells generated from bone marrow precursor cells (BMPC) from young or aged mice in young hosts. In two different models, memory cells derived from young and aged BMPC exhibit good ex vivo and in vivo function. Importantly, memory CD4 T cells generated from aged BMPC exhibit potent cognate helper function for humoral responses, which are critical for effective immunization. These results indicate that there are no apparent age-related intrinsic defects in BMPC with regards to generation of functional memory T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health-National Institute of Aging Grants AG02160 and AG025805.

² Address correspondence and reprint requests to Dr. Laura Haynes, Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983. E-mail address: lhaynes{at}trudeauinstitute.org

³ Abbreviations used in this paper: BMPC, bone marrow precursor cell; Tg, transgenic; PCC, pigeon cytochrome c; 4-hydroxy-3-nitrophenyl acetyl (NP); PNA, peanut agglutinin; GFP, green fluorescence protein; GC, germinal center.